Reduced-intensity conditioning (RIC) regimens are increasingly used for allogeneic stem cell transplantation (allo-SCT). RIC has been shown to allow engraftment with minimal early transplantationrelated mortality (TRM). However, in the context of RIC, predictive factors for acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively) and their effect on outcome remain unknown. In this report, we analyzed the outcome of 101 high-risk patients (70 hematologic and 31 nonhematologic malignancies) who received an HLA-identical sibling allo-SCT after RIC, including fludarabine, busulfan, and antithymocyte globulin (ATG). The cumulative incidence of grade II-IV aGVHD was 36% (95% confidence interval [CI], 27%-45%), whereas the cumulative incidence of cGVHD at 2 years was 43% (95% CI, 33%-53%). In multivariate analysis, the incidence of aGVHD was significantly associated with the ATG dose infused during conditioning (P ؍ .0005), whereas peripheral blood as stem cell source was the only predictive factor for the development of cGVHD (P ؍ .0007). The 1-year cumulative incidences of disease progression or relapse in patients with (n ؍ 69) and without (n ؍ 31) GVHD (whatever its form or grade) were 30% (95% CI, 19%-41%) and 55% (95% CI, 37%-72%), respectively (P ؍ .02), suggesting that a potent graft-versus-tumor (GVT) effect can be achieved in high-risk patients following RIC. Moreover, the GVT effect was closely associated with GVHD without an increased risk of TRM (cumulative incidence of TRM, 18% [95% CI, 10%-25%]). Collectively, these results provide a framework for the refinement of RIC approaches designed to enhance the GVT effect with an acceptable risk of GVHD.
This survey demonstrates that AEs occurring in the setting of DMSO-reduced HPC grafts are directly related to the amount of granulocytes and thus emphasizes the need for high-quality apheresis products so as to improve the safety of HPC infusion.
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